Open Veterinary Journal, (2023), Vol. 13(7): 942-947
ISSN: 2226-4485 (Print)
ISSN: 2218-6050 (Online)

Submitted: 12/04/2023

Original Research
DOI: 10.5455/OVJ.2023.v13.i7.14

Accepted: 19/06/2023

Published: 31/07/2023

Effects of high-dose docosahexaenoic acid supplementation as an add-on
therapy for canine idiopathic epilepsy: A pilot study
Tomohiro Yonezawa*, Cris Niño Bon B. Marasigan , Yuki Matsumiya
Tomoki Motegi
and Yasuyuki Momoi, Shingo Maeda,

Laboratory of Veterinary Clinical Pathobiology, Department of Veterinary Medical Sciences, Graduate Schoolof Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan
Abstract
Background: The anti-epileptic effects of docosahexaenoic acid (DHA) in dogs and humans remain controversial.
The dosage and efficacy of DHA were various in the previous reports.
Aim: The effects of high-dose DHA supplementation as add-on therapy for idiopathic epilepsy in dogs were evaluated.
Methods: An open-label clinical trial was designed in this pilot study. Six dogs (median age: 6 years) with idiopathic
epilepsy were included. All the patients were diagnosed with idiopathic epilepsy using magnetic MRI and cerebrospinal
fluid examination (median: 2.0 years before the trial). They had 5–45 seizures and/or auras (median: 9.0) in the month
before starting DHA supplementation. DHA was adjunctively administered at doses of 69–166 mg/kg/day withoutchanging other prescriptions.
Results: Four of the six patients completed the 6-month observation period. All the patients showed a decrease inseizure frequency of 50% or more within 2–3 months after the start of the administration, and three patients decreased
to a frequency of 0–1 per month after 5–6 months. No clear adverse events were observed in the general condition or
blood test results in any patients.
Conclusion: Although the sample size was small and the study was not a randomized controlled trial, the data suggestthat add-on supplementation of DHA could be useful in reducing the frequency of seizures in canine idiopathic epilepsy.
Keywords: Docosahexaenoic acid, Dogs, Drug-resistant epilepsy, Idiopathic epilepsy, Omega-3 fatty acids.

Introduction
In dogs, idiopathic epilepsy is a condition of repeatedseizures in which there are no organic lesions in thebrain and no clear origin of the seizures (Berendt etal., 2015). This form of epilepsy is one of the mostcommon chronic neurological disorders observedin dogs. Although prevalence varies depending on
the study, it has been reported to be from 0.62% to1.84% (Kearsley-Fleet et al., 2013; Heske et al., 2014;
Hamamoto et al., 2016). The International Veterinary
Epilepsy Task Force published a consensus statement
regarding the treatment of idiopathic epilepsy in dogs
(Sofie et al., 2015). In many cases, the frequency of
seizures can be sufficiently reduced by prescribing
antiepileptic drugs (AEDs) according to guidelines.
However, in less than 30% of these cases, the frequency
and severity of seizures cannot be reduced even withmultiple AEDs (Trepanier et al., 1998). Therefore, thedevelopment of medications that support the action of
AEDs has garnered significant research attention withthe goal of improving quality of life.

Docosahexaenoic acid (DHA) is an omega-3 fatty acidabundantly found in blue fish and crustaceans. Although
DHA intake is known to have a positive effect on brain
function (Lauritzen et al., 2016), its association withneural diseases such as epilepsy remains controversial.
In a 2018 systematic review, four of nine studies
in human patients reported a significant positive
association between omega-3 fatty acids and epileptic
seizures; however, the authors could not conclude abeneficial effect because of the low statistical power(Pourmasoumi et al., 2018). Another clinical study of
99 patients reported that the administration of DHA at adose of approximately 33.4–49.1 mg/kg/day reduced thefrequency of seizures in patients with refractory epilepsy(Ibrahim et al., 2018). Two papers have been published on
the administration of omega-3 fatty acids for idiopathic
epilepsy in dogs; however, the AEDs of DHA have notbeen clearly indicated (Scorza et al., 2009; Matthews etal., 2012). In these studies, dogs were administered 2 g/head/day of whole omega 3 fatty acid and 25 mg/kg/dayof DHA, respectively, which were lower doses than thosereported in humans, and the ratio of DHA components
to fatty acids was ambiguous in one study (Scorza et*Corresponding Author: Tomohiro Yonezawa. Laboratory of Veterinary Clinical Pathobiology, Department of Veterinary
Medical Sciences, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.
Email: tomohiro.yonezawa@gmail.com
Articles published in Open Veterinary Journal are licensed under a Creative Commons Attribution-NonCommercial 4.0 International License942

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T. Yonezawa et al.Open Veterinary Journal, (2023), Vol. 13(7): 942-947

al., 2009). In addition, the NOAEL of DHA + EPA in
healthy dogs has been reported to be sufficiently higher
than these doses (Takeda Pharmaceutical Company,
2020), suggesting that DHA can be safely administeredat higher doses than those reported in previous studies.
Therefore, we conducted an open-label clinical trial toclarify the effects of supplemental treatment with a highdose of DHA in dogs with idiopathic epilepsy.

activity. Clinical pathology, including routine complete
blood count, alanine aminotransferase (ALT), alkaline
phosphatase (ALP), blood urea nitrogen (BUN), andcreatinine (CRE) was assessed every 3 months forclinical assessment. Total cholesterol (TCHO) andtriglyceride (TG) were obtained from one patient.
Routine blood examinations were performed by aveterinarian using a ProCyte Dx hematology analyzer(IDEXX Laboratories, MA, USA) and DRI-CHEM
7000V (FUJIFILM VET Systems, Tokyo, Japan).
As humane endpoints, any animal that showed negative
reactions to supplementation was withdrawn. The
dropout criteria were defined as follows: occurrence ofstatus epilepticus and/or cluster seizures; critically poor
general physical condition; loss of more than 5% of
total body weight post-administration; the presence ofremarkable clinical pathology results; non-compliancewith DHA administration; and owner withdrawal.
Statistical analysis
All statistical analyses were conducted using XLSTATLife Science (version 2021.2.2.1141, Addinsoft, Paris,
France) as an add-on application in Microsoft Excel(Microsoft Corporation, Redmond, Washington, DC).
Friedman and Nemenyi post-hoc tests were used
to compare the time periods. No missing data were
imputed. The significance level was set at p-value<0.05.
Ethical approval
This open-label prospective canine clinical trial was
conducted at the Veterinary Medical Center, Universityof Tokyo (Tokyo, Japan), following approval fromthe ethics and welfare committee of the center(#VMC2018-5).

Materials and Methods
Inclusion criteria
Animals that had been in regular follow up at thecenter were enrolled in the trial between 2019 and 2021
(Table 1). The inclusion criteria were as follows: 1- to
10 -year-old dogs; clinically diagnosed with idiopathic
epilepsy; that had been on AEDs at the same dose(s) forat least 2 months; and had seizure and/or aura episodes
more than twice per month. The diagnosis of idiopathic
epilepsy (with a Tier II confidence level) was concludedin accordance with the guidelines of the International
Veterinary Epilepsy Task Force (De Risio et al., 2015)
as follows: absence of neurological abnormalities during
the interictal period; unremarkable results of cranial MRI
examination; and reactive seizures ruled out via medical
records, physical examination, and blood examination.
As part of the selection process, the trial was discussedwith the owners, and consent was obtained. Six dogs
were identified as fit and enrolled in the trial (Table 1).
Procedure
DHA supplements (DHA70 BAPT, Bizen Chemical,
Okayama, Japan) were prescribed at a dose of 50–100
mg/kg to be taken every 12 hours (100–200 mg/kg/day)for 6 months. The DHA capsules were oval in shape,
measuring 13 mm long and 7.5 mm in diameter. During
the trial period, the owners were advised to continue
administering AEDs that had been prescribed prior to
the study. Follow-up visits were performed each month
to check for the following: seizure episodes, vital signs,
physical assessment, and changes in patient behavior/

Results
Six dogs were initially enrolled in this study, as shownin Table 1. Four patients had a history of generalized
tonic-clonic seizures, while the other two had recurrent
focal motor seizures in the forelimbs. All patients wereTable 1. Patient characteristics and AED doses.
Case

Breeding

Age(year)

Sex

BW
(kg)

Seizure type

Period fromdiagnosis

Doses of AEDs
(mg/kg, twice daily)

1Chihuahua

3

M

2.0

Tonic-clonic

1.5 year

ZNS 10, PGB 4.1,
LEV 20.8, KBr 25

2

Shetland
Sheepdog

7

nF

17

Tonic-clonic

3 years

PB 2.6, ZNS 11.6

3

Toy Poodle

9

nM

6.5

Focal motor
seizures

2.5 years

LEV 9.2, KBr 15.5

4

Toy Poodle

6

nM

4.0

Focal to bilateral
tonic-clonic

4 years

ZNS 3.8

5

Pomeranian

2

F

2.5

Focal motor
seizures

1 yearZNS 4

6

Saluki

6

nF

21

Tonic-clonic

3 months

ZNS 7.1(M): male; (F): female; (nM): neutered male; (nF): neutered female.

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T. Yonezawa et al.Open Veterinary Journal, (2023), Vol. 13(7): 942-947

diagnosed with idiopathic epilepsy using MRI and
CSF tests following the guidelines under the Tier II
confidence level for diagnosing idiopathic epilepsy indogs. The median age of the animals was 6 years (range:
2–9 years), and the median period of diagnosis was 2.0
years before the start of the trial (range: 3 months to 4
years). Doses and responses to DHA supplementation
are shown in Table 2. With a median dose of 121.8
mg/kg/day (range: 69.1–166 mg/kg/day), five patients
received oral DHA capsules twice daily, whereas theremaining patient only received the capsule once daily
due to a misunderstanding. One patient withdrew fromthe program due to inconsistent adherence to the trial
protocol, and another withdrew due to changes inprimary AED medication.
The assessment of seizure activity revealed that all
remaining animals receiving DHA supplementation
showed improvements in the frequency and severity of
seizures and auras (Table 2). They had 5–45 seizures
and/or auras (median: 9) within 1 month of starting
DHA supplementation. They were treated at doses of
41.5 to 83 mg/kg once or twice daily in total 69.1 to166 mg/kg/day of DHA (median, 109.2 mg/kg/day).
Four of the six dogs completed the 6-month observed
period without changes in medication. The seizure
frequencies of all patients decreased by 50% or moreby 2–3 months after the start of DHA supplementation,and those of three patients decreased to 0–1 permonth at 5–6 months. Statistical analyses using theFriedman test (p = 0.00249) showed differences inseizure frequency among the groups at the time of thetrial. Further analyses using the Nemenyi post-hoc
test (p = 0.0338) revealed that the total frequency of
seizures and auras was significantly different between
the pre-trial period and at 5 months after the start of
supplementation. The results of body weight and blood

examination tests are shown in Table 3. Adverse events
related to supplementation were not observed in any
cases. No problems were identified during physicalexaminations or follow-up interviews.
Two patients had to be withdrawn from the trial. Case
5 was a 2-year-old intact female Pomeranian dog witha history of focal motor seizures. She was administeredoral DHA supplementation at an inappropriate doseof 69.1 mg/kg once daily instead of twice due tomiscommunication. Owing to the size of the DHA
capsule, the owner struggled to administer it. The
veterinarian advised the owner to decapsulate it and mix
the contents with the feed; however, it appeared that thepatient missed the appropriate amount of DHA despite
multiple attempts during the observation period. The
owners were not able to record the precise number of
seizures at the time of the trial but felt that the severity
and frequency of seizures decreased. After consultingwith a veterinarian, the patient withdrew from theprogram. Case 6, a 6-year-old neutered female Saluki
dog with tonic-clonic seizures, was also excluded fromthe trial due to an alteration in AED medication. Prior
to withdrawal, the seizure activity of the patient had
apparently reduced at a dose of 63.2 mg/kg twice daily.
Discussion
In this study, an open-label clinical trial was conductedon six dogs with idiopathic epilepsy. Four of the six
patients completed the 6-month observed period
without changes in their primary AED regimens. All
dogs showed a decrease in seizure frequency of 50%
or more at 2–3 months after the start of administration,and three of the four dogs decreased to 0–1 per monthat the end of the study period. These data suggest that
DHA may be a useful supplement for treating canine
idiopathic epilepsy. While statistical changes wereTable 2. Effects of DHA supplementation on seizure frequency.
Case

Doses of DHA

Frequency of seizures(mg/kg)per dayPre

1 month 2 months 3 months 4 months 5 months 6 months

1

83

2

4
(8)

3
(2)

1
(3)

2
(0)

1
(0)

0
(0)

0
(0)

2

58.5

2

3
(2)

2
(0)

0
(2)

2
(1)

0
(1)

0
(1)

1
(0)

4

50.7

2

45

48

29

14

8

5

11

3

83.0

2

6
(0)

6
(0)

7
(3)

2
(0)

2
(0)

0
(1)

0

5

69.1

1

20

20*

20*

D.O.

6

63.2

2

5

2

0

D.O.

(*): duration of seizure was improved; Parentheses, the number of aura; (D.O.): dropped out (see the Result).

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T. Yonezawa et al.Open Veterinary Journal, (2023), Vol. 13(7): 942-947

Table 3. Pre- and post-supplementation body weights and test results.
Case

1

2

3

4

5

6

Time after
DH3A
supplementation

BW
(kg)

Pre

2.04

3 months

2.14

Platelets(K/µl)

ALT
(U/l)

ALP
(U/l)

BUN
(mg/dl)CRE(mg/dl)TCHO(mg/dl)TG(mg/dl)(14.8–48.4)(17–78)(<254)(9.2–29.2)(0.40–1.40)(111–312)(30–133)

56.4

91

256

17.5

0.37

N.D.

N.D.

66.6

132

235

14.9

0.35

N.D.

N.D.

6 months

2.06

47.6

116

245

12.7

0.35

N.D.

N.D.

Pre

18.1

41.4

91

>3,500

13.7

0.73

N.D.

N.D.

3 months

18.5

N.D.

138

>3,500

10.3

0.67

N.D.

N.D.

6 months

18.6

47.2

96

2,762

13.0

0.62

N.D.

N.D.

Pre

3.88

47.1

69

266

24.6

0.75

N.D.

N.D.

3 months

3.96

45.0

81

272

16.2

0.45

N.D.

N.D.

6 months

3.82

34.7

86

211

21.8

0.58

N.D.

N.D.

Pre

6.46

33.3

91

67

N.D.

N.D.

212

36

3 months

6.76

37.4

110

118

N.D.

N.D.

210

119

6 months

6.8

26.8

126

124

N.D.

N.D.

211

192

Pre

2.52

28.6

37

174

27.0

1.10

N.D.

N.D.

3 months

2.48

37.0

30

148.0

19.3

0.66

N.D.

N.D.

6 months

-

-

-

-

-

-

-

-

Pre

21.8

7.7

173

175

16.5

0.94

N.D.

N.D.

3 months

21.8

7.0

N.D.

N.D.

N.D.

N.D.

N.D.

N.D.

6 months

-

-

-

-

-

-

-

-

Ranges, reference intervals; (N.D.) not determined; (-): not followed.

observed, the sample size was small, and the power
was quite low. A large-scale trial is needed to verify theeffectiveness of DHA as a supplement for idiopathic
epilepsy in dogs.
There have been few reports on DHA administration indogs with idiopathic epilepsy showing a clear effect. In
2009, a 2-year-old Great Dane with idiopathic epilepsy
was treated with 2 g/head/day of omega-3 fatty acids
derived from fish oil (Scorza et al., 2009). The bodyweight of the dog was not reported. The seizure
frequency decreased from 2 to <1 within 2–3 months.
Although this result suggests that omega-3 fatty acids
could be effective for idiopathic epilepsy in dogs, thedosage was unclear, and the proportion of DHA in theomega-3 fatty acids was not indicated. In another reportby Matthews et al. (2012) 40 mg/kg EPA, 25 mg/kg
DHA, and 2.2 mg/kg vitamin E were administered to
15 dogs with idiopathic epilepsy treated with AEDs
for 12 weeks. While no adverse effects were observed,
there was no clear decrease in seizure frequency orseverity. In this study, all patients were administered
DHA at doses of 69 to 166 mg/kg/day, which was morethan two to six times higher than those used in previous
studies, including in human reports (Ibrahim et al.,2018; Pourmasoumi et al., 2018). Moreover, the DHA/
EPA ratio was higher than that previously reported.
The high dose and purity of DHA could be one of thereasons for its high efficacy in this study. There aresimilarities in the pathogenesis and pathophysiology ofcanine and human epilepsy (Chandler, 2006), implyingthat research on canine patients could be translated totreatment in humans. The present data also indicate thescope for reconsidering effective dosages of DHA in
human patients with epilepsy.
The mechanism by which DHA reduces seizure
frequency in epilepsy is not well understood. In reports
using the epileptic mice model, DHA is suggested
to increase serotonin secretion, promote serotoninreceptors in postsynaptic membranes, and increaseneurosteroid secretory activity (Patrick and Ames,
2015; Ishihara et al., 2017). In addition, omega-3
fatty acids, such as DHA, are abundant in nerve cells
in the cerebral cortex and are known to increase thefluidity of cell membranes and cell plasticity (Lauritzen
et al., 2016). DHA also reduces the inward calcium
currents and prolongs the inactivated state of cells after
action potentials (Xiao et al., 1997). Identifying themechanism of action of DHA was beyond the scopeof this study. However, our findings provide evidence
regarding its positive effect and are expected to support
future research analyzing the physiological effects of
DHA in epilepsy.
The efficacy of DHA tended to be observed
approximately 1–3 months after the start of treatment,
and statistically significant differences were observed
5 months after the start of treatment. This is consistent945

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T. Yonezawa et al.with the results of a previous study in patients withepilepsy (Ibrahim et al., 2018). In the body, DHA
function is dependent on dietary supply (Gao et al.,2009). DHA is first trapped in low-density lipoprotein(LDL) pools, and the free form of DHA is systemicallyreleased after the LDL pool is saturated (Taha et al.,2010). It has been reported that the concentration of
DHA in the CSF increases after consistent dietaryintake (Levi et al., 2014). These distribution systems
may take a long time to exert the antiepileptic effectsof DHA.
There are several known adverse effects of DHA in
humans. The DHA/EPA preparation omega-3 fatty
acid ethyl (Lotriga, Takeda Pharmaceutical Company,
Tokyo, Japan) was approved in 2012 for hyperlipidemia
treatment. According to the interview form, 948 adults
were treated with 2 or 4 g of triga. Of these, 91 (9.6%)
had adverse effects, mainly diarrhea (2.5%) (Takeda
Pharmaceutical Company, 2020). As other serious
side effects, the elevation of AST, ALT, AL-P, γ-GTP,
LDH, bilirubin, etc. has been suggested (Takeda
Pharmaceutical Company, 2020). In a clinical trial of
DHA administration in pediatric epilepsy reported by
Ibrahim et al. (2018) loss of appetite, fever, and rashwere observed by treatment of not only EPA or DHA
but also placebo. In addition, DHA and EPA are known
to have anticoagulant effects (Swanson et al., 2012),
suggesting that they should be used with caution inpatients with diseases associated with a high risk of
bleeding and in those taking anticoagulants. A repeateddose toxicity study using healthy adult dogs was
conducted using Lotriga’s interview form. According to
one report, the NOAEL was >1,000 mg/kg/day for over
52 weeks (Takeda Pharmaceutical Company, 2020). As
the DHA content of the drug is approximately 36.7%(Takeda Pharmaceutical Company, 2020), >367 mg/kg/
day of DHA is estimated to be the NOAEL in dogs. Mild
suppression of body weight gain was observed withoutchanges in food consumption or coat contamination(Takeda Pharmaceutical Company, 2020). In anotherstudy, the breath smell worsened (Scorza et al.,2009). However, no side effects suggestive of severe
abnormalities were observed in any of the dog. In thisstudy, no adverse effects were observed during theobservation period. Nevertheless, based on previous
reports, it is better to continue paying close attention to
gastrointestinal symptoms, liver disorders, coagulation
systems, body weight, and coating conditions.
This study had several limitations. This was a pilot
study, and the reproducibility of the results is notguaranteed, although the findings were found to bestatistically significant. Because the test was designed
as an open-label trial rather than a blind test, it is subject
to owner and observer biases. A control group was notincluded because of ethical considerations. The otherprescriptions, except for DHA, did not change from 2
months before the start of the trial to the end; however,

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Open Veterinary Journal, (2023), Vol. 13(7): 942-947

this does not completely account for the possibility that
seizure symptoms were improved by drugs other than
DHA during the observation period.
Conclusion
This pilot study investigated the potential of highdose DHA preparation as an ancillary treatment forcanine idiopathic epilepsy. After several months ofsupplementation, the frequency of seizures and auras
decreased without any apparent adverse effects. A
large-scale study will likely prove its effectiveness as asupplement in idiopathic epilepsy.
Acknowledgments
DHA70 BAPT was a gift from Bizen Chemicals. We
are grateful to Dr. Yoshihisa Misawa for coordinating
the supply of formulations.
Conflict of interest
The authors declare that this study was conducted in theabsence of any commercial or financial relationshipsthat could be construed as potential conflicts of interest.
Funding
The authors received no financial support for the
research.
Availability of data
The datasets analyzed during the current study
are available from the corresponding author upon
reasonable request.
Author contributions
Conceptualization, TY; Methodology, TY, CNBBM,
YM; Validation, CNBBM, YM; Statistical Analysis,
TY, TM; Resources, SM, TM, YM; Data Curation,
TY; Writing – Original Draft Preparation, CNBBM;
Review and Editing, TY; Supervision, TY; Project
Administration, TY.
References
Berendt, M., Farqhuar, R.G., Mandigers, P.J.J., Pakozdy,
A., Bhatti, S.F.M., De Risio, L., Fischer, A., Long, S.,
Matiasek, K., Muñana, K., Patterson, E.E., Penderis,J., Platt, S., Podell, M., Potschka, H., Pumarola,M.B., Rusbridge, C., Stein, V.M., Tipold, A. andVolk, H.A. 2015. International veterinary epilepsy
task force consensus report on epilepsy definition,
classification and terminology in companion
animals. BMC. Vet. Res. 11, 182–192.
Chandler, K. 2006. Canine epilepsy: what can welearn from human seizure disorders? Vet. J. 172(2),207–217.
De Risio, L., Bhatti, S., Muñana, K., Penderis, J.,
Stein, V., Tipold, A., Berendt, M., Farqhuar, R.,
Fischer, A., Long, S., Mandigers, P.J., Matiasek,
K., Packer, R.M., Pakozdy, A., Patterson, N.,
Platt, S., Podell, M., Potschka, H., Batlle, M.P.,
Rusbridge, C. and Volk, H.A. 2015. International
veterinary epilepsy task force consensus proposal:
diagnostic approach to epilepsy in dogs. BMC.
Vet. Res. 11, 148.

http://www.openveterinaryjournal.com
T. Yonezawa et al.Gao, F., Kiesewetter, D., Chang, L., Ma, K., Bell, J.M.,
Rapoport, S.I. and Igarashi, M. 2009. Whole-bodysynthesis-secretion rates of long-chain n-3 PUFAs
from circulating unesterified alpha-linolenic acidin unanesthetized rats. J. Lipid. Res. 50(4), 749–
758.
Hamamoto, Y., Hasegawa, D., Mizoguchi, S.,
Yu, Y., Wada, M., Kuwabara, T., FujiwaraIgarashi, A. and Fujita, M. 2016. Retrospective
epidemiological study of canine epilepsy in Japan
using the International veterinary epilepsy task
force classification 2015 (2003-2013): etiologicaldistribution, risk factors, survival time, and lifespan.
BMC. Vet. Res. 12(1), 248.
Heske, L., Nødtvedt, A., Jäderlund, K.H., Berendt, M.
and Egenvall, A. 2014. A cohort study of epilepsy
among 665,000 insured dogs: incidence, mortality
and survival after diagnosis. Vet. J. 202(3), 471–476.
Ibrahim, F.A.S., Ghebremeskel, K., Abdel-Rahman,
M.E., Ahmed, A.A.M., Mohmed, I.M., Osman,G., Elseed, M., Hamed, A., Rabinowicz, A.L.,
Salih, M.A.M., Elbashir, M.I. and Daak, A.A.
2018. The differential effects of eicosapentaenoic
acid (EPA) and docosahexaenoic acid (DHA) on
seizure frequency in patients with drug-resistant
epilepsy—a randomized, double-blind, placebocontrolled trial. Epilepsy. Behav. 87, 32–38.
Ishihara, Y., Itoh, K., Tanaka, M., Tsuji, M., Kawamoto,T., Kawato, S., Vogel, C.F.A. and Yamazaki, T.
2017. Potentiation of 17beta-estradiol synthesis in
the brain and elongation of seizure latency throughdietary supplementation with docosahexaenoic
acid. Sci. Rep. 7(1), 6268.
Kearsley-Fleet, L., O'Neill, D.G., Volk, H.A., Church,
D.B. and Brodbelt, D.C. 2013. Prevalence and risk
factors for canine epilepsy of unknown origin in the
UK. Vet. Rec. 172(13), 338.
Lauritzen, L., Brambilla, P., Mazzocchi, A., Harsløf,
L.B.S., Ciappolino, V. and Agostoni, C. 2016.
DHA effects in brain development and function.
Nutrients 8(1), 6.
Levi, Y.F., Vedin, I., Cederholm, T., Basun, H., Irving,
G.F., Eriksdotter, M., Hjorth, E., Schultzberg,
M., Vessby, B., Wahlund, L.O., Salem, Jr. N. andPalmbladr, J. 2014. Transfer of omega-3 fatty
acids across the blood-brain barrier after dietary
supplementation with a docosahexaenoic acid-richomega-3 fatty acid preparation in patients with
Alzheimer's disease: the OmegAD study. J. Intern.
Med. 275(4), 428–436.

Open Veterinary Journal, (2023), Vol. 13(7): 942-947

Matthews, H., Granger, N., Wood, J. and Skelly, B.
2012. Effects of essential fatty acid supplementationin dogs with idiopathic epilepsy: a clinical trial. Vet.
J. 191(3), 396–398.
Patrick, R.P. and Ames, B.N. 2015. Vitamin D and theomega-3 fatty acids control serotonin synthesis
and action, part 2: relevance for ADHD, bipolar
disorder, schizophrenia, and impulsive behavior.
FASEB. J. 29(6), 2207–2222.
Pourmasoumi, M., Vosoughi, N., DerakhshandehRishehri, S.M., Assarroudi, M. and Heidari-Beni,
M. 2018. Association of omega-3 fatty acid andepileptic seizure in epileptic patients: a systematic
review. Int. J. Prev. Med. 9, 36.
Scorza, F.A., Cavalheiro, E.A., Arida, R.M., Terra,
V.C., Scorza, C.A., Ribeiro, M.O. and Cysneiros,
R.M. 2009. Positive impact of omega-3 fatty
acid supplementation in a dog with drug-resistant
epilepsy: a case study. Epilepsy. Behav. 15(4),527–528.
Sofie, F.M., De Risio, B.L., Muñana, K., Penderis, J.,
Stein, V.M., Tipold, A., Berendt, M., Farquhar, R.G.,
Fischer, A., Long, S., Löscher, W., Mandigers, P.J.J.,
Matiasek, K., Pakozdy, A., Patterson, E.E., Platt, S.,
Podell, M., Potschka, H., Rusbridge, C. and Volk,
H.A. 2015. International veterinary epilepsy task
force consensus proposal: medical treatment ofcanine epilepsy in Europe. BMC. Vet. Res. 11, 176.
Swanson, D., Block, R. and Shaker, A. 2012. Omega-3
fatty acids EPA and DHA: health benefits
throughout life. Adv. Nutr. 3(1), 1–7.
Taha, A.Y., Burnham, W.M. and Auvin, S. 2010.
Polyunsaturated fatty acids and epilepsy. Epilepsia
51(8), 1348–1358.
Takeda Pharmaceutical Company. 2020. EPA/DHA
pharmaceutical formulation; Lotriga granular
capsule 2 g. Pharmaceutical interview form.Available
via https://www.takedamed.com/mcm/medicine/
download.jsp?id=152&type=INTERVIEW_FORM
Trepanier, L.A., Schoick, A.V., Schwark, W.S.
and Carrillo, J. 1998. Therapeutic serum drugconcentrations in epileptic dogs treated withpotassium bromide alone or in combination withother anticonvulsants: 122 cases (1992–1996). J.
Am. Vet. Med. Assoc. 213(10), 1449–1453.
Xiao, Y.F., Gomez, A.M., Morgan, J.P., Lederer, W.J.
and Leaf, A. 1997. Suppression of voltage-gated
L-type Ca2+ currents by polyunsaturated fatty
acids in adult and neonatal rat ventricular myocytes.
Proc. Natl. Acad. Sci. U.S.A. 94(8), 4182–4187.

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